SIMPLIFY-1 phase III post hoc analysis: Momelotinib vs ruxolitinib in JAKi-naïve anemic MF

Results from a post hoc analysis of the multicenter, double-blind, randomized phase III SIMPLIFY-1 (NCT01969838) trial, evaluating momelotinib vs ruxolitinib in patients with Janus kinase (JAK) inhibitor-naïve myelofibrosis (MF) and anemia, were published in Clinical Lymphoma, Myeloma & Leukemia by Palandri et al. The analysis included patients with baseline hemoglobin <10 g/dL (N = 180; momelotinib, n = 86; ruxolitinib, n = 94). The original primary endpoint was spleen volume reduction ≥35% (SVR35) at Week 24; this analysis evaluated Week 24 SVR35, transfusion independence (TI), dual response (SVR35 + TI), and the association of these outcomes with overall survival (OS) in the momelotinib arm. 

Key data: At Week 24, SVR35 rates were similar with momelotinib vs ruxolitinib (31% vs 33%), while dual response was higher with momelotinib (27% vs 7%). In patients with baseline platelets <200 × 10⁹/L, Week 24 rates of SVR35 (39% vs 17%), TI (51% vs 21%), and dual response (33% vs 2%) were higher with momelotinib vs ruxolitinib. Conversely, SVR35 rates were higher with ruxolitinib vs momelotinib in patients with baseline platelets ≥200 × 10⁹/L (22% vs 49%). With momelotinib, OS was longer with TI alone (hazard ratio [HR], 0.25) or dual response (HR, 0.40) vs neither, while SVR35 alone was not clearly associated with longer OS (HR, 0.80). In multivariate analysis, TI remained independently associated with longer OS (HR, 0.33; p = 0.0085), while SVR35 did not (HR, 1.13; p = 0.777). 

Key learning: In patients with JAKi-naïve myelofibrosis and anemia, momelotinib demonstrated comparable spleen response and higher dual response vs ruxolitinib at Week 24, with benefits most pronounced in patients with platelets <200 × 10⁹/L. TI at Week 24 was the strongest predictor of longer OS, supporting consideration of momelotinib as a preferred JAKi in this population.